Mayzent (siponimod) belongs to a class of medications called sphingosine l-phosphate receptor modulators.

Mayzent is used to prevent episodes of symptoms and slow the worsening of disability in adults with relapsing-remitting forms (course of disease where symptoms flare up from time to time) of multiple sclerosis (MS); a disease in which the nerves do not function properly and people may experience weakness, numbness, loss of muscle coordination, and problems with vision, speech, and bladder control).

Mayzent works by decreasing the action of immune cells that may cause nerve damage.

Mayzent is used only if you have a specific genotype. Your doctor will test you for this genotype.

You should not use Mayzent if you have a serious heart condition such as "sick sinus syndrome" or "AV block" (unless you have a pacemaker), or if you've recently had heart block, heart failure, a heart rhythm disorder, chest pain, heart attack, or stroke.

Mayzent can slow your heart rate when you start taking it. You may receive your first dose in a setting where your heart rhythm can be monitored. If you miss any doses, you may need to restart taking this medicine under medical observation.

You may get infections more easily, even serious or fatal infections. Call your doctor if you have a fever, chills, aches, tiredness, vomiting, confusion, neck stiffness, or problems with coordination, thought, vision, or muscle movement. Your risk of infection could last for 3 to 4 weeks after you stop taking this medicine.

You may have increased sensitivity to light, blurred vision, eye pain, or have a blind spot or shadows in the center of your vision, unusual color to your vision, or other vision problems while you are taking Mayzent, which may occur 1 to 4 months after your first dose.

You should not use Mayzent if you have a specific genotype. Your doctor will perform tests to make sure this medicine is the right treatment for you.

Take Mayzent exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your dose will be increased gradually during the first 5 to 6 days of taking Mayzent.

You may need medical tests before you start taking Mayzent including blood tests, ECG, eye evaluation, heart and liver function tests, and skin exam.

Siponimod can slow your heart rate when you start taking it. You may receive your first dose in a medical setting. Your blood pressure and heart rate may be constantly monitored for at least 6 hours after your first dose of Mayzent.

Siponimod affects your immune system. You may get infections more easily, even serious or fatal infections. Your doctor will need to examine you on a regular basis. Your risk of infection could last 3 to 4 weeks after you stop taking this medicine.

Always ask your doctor before you stop taking Mayzent for any reason. When you stop taking Mayzent, your MS symptoms may return. In rare cases, some people who stopped taking Mayzent had MS symptoms that were worse than before or during treatment with this medicine.

If you stop taking Mayzent, do not start taking it again without asking your doctor. You may need to be under medical observation when you restart this medication.

Do not crush, break, or split a Mayzent tablet. Swallow the tablet whole.

You may take Mayzent with or without food.

Store unopened tablets in the refrigerator, do not freeze.

After opening, store Mayzent in the original container at room temperature away from moisture and heat for up to 3 months.

If you stop taking this medicine, watch for signs of worsening MS, and call your doctor right away if any new or worsening symptoms appear.

Usual Adult Dose for Multiple Sclerosis:

CYP450 2C9 Genotype *1/*1, *1/*2, or *2/*2:
-Titration regimen: 0.25 mg orally once daily on Days 1 and 2, then 0.5 mg orally once daily on Day 3, then 0.75 mg orally once daily on Day 4, then 1.25 mg orally once daily on Day 5
-Maintenance dose: 2 mg orally once daily beginning on Day 6
NOTE: Use a starter pack for patients who will be titrated to the 2 mg maintenance dose.

CYP450 2C9 Genotype *1/*3 or *2/*3:
-Titration regimen: 0.25 mg orally once daily on Days 1 and 2, then 0.5 mg orally once daily on Day 3, then 0.75 mg orally once daily on Day 4
-Maintenance dose: 1 mg orally once daily beginning on Day 5
NOTE: Do not use the starter pack for patients who will be titrated to the 1 mg maintenance dose.
-If one titration dose is missed for more than 24 hours, therapy needs to be reinitiated with Day 1 of the titration regimen.

Comments:
-If one titration dose is missed for more than 24 hours, therapy needs to be reinitiated with Day 1 of the titration regimen.
-First-dose monitoring is recommended for patients with sinus bradycardia, first- or second-degree atrioventricular (AV) block, or a history of myocardial infarction or heart failure.
-Administer the first dose in a setting equipped to manage symptomatic bradycardia.
-Monitor patients for 6 hours after the first dose for bradycardia with hourly pulse and blood pressure measurements. Obtain an ECG in these patients at the end of Day 1.
-If any of the following abnormalities are present after 6 hours (even in the absence of symptoms), continue monitoring until the abnormality resolves: the heart rate 6 hours post dose is less than 45 bpm; the heart rate 6 hours post dose is at the lowest value post dose, suggesting that the maximum pharmacodynamic effect on the heart may not have occurred; the ECG 6 hours post
dose shows new onset second-degree or higher AV block.
-If post dose symptomatic bradycardia, bradyarrhythmia, or conduction related symptoms occur, or if ECG 6 hours post dose shows new onset second degree or higher AV block or QTc greater than or equal to 500 msec, initiate management, begin continuous ECG monitoring, and continue monitoring until the symptoms have resolved if no treatment is required. If treatment is required, continue monitoring overnight and repeat 6-hour monitoring after the second dose.
-After the initial titration is complete, if treatment is interrupted for 4 or more consecutive daily doses, reinitiate therapy with Day 1 of the titration regimen; also complete first-dose monitoring in patients for whom it is recommended.

Use: For relapsing forms of multiple sclerosis (MS) including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults

You should not use Mayzent if you are allergic to siponimod or any of the ingredients in Mayzent tablets, or if you have:

• a specific genotype;

• "AV block" (2nd or 3rd degree);

• irregular or abnormal heart rhythm (unless you have a pacemaker); or

• recent (within the past 6 months) heart failure, heart attack, stroke, 'mini-stroke' or TIA, chest pain (unstable angina), or other serious heart problem.

Some heart rhythm medications can cause unwanted or dangerous effects when used with Mayzent. Your doctor may change your treatment plan if you also use: amiodarone, disopyramide, dofetilide, dronedarone, flecainide, ibutilide, procainamide, propafenone, quinidine, or sotalol.

Before you take Mayzent, tell your doctor if you have never had chickenpox or if you have never received a varicella vaccine. You may need to receive the vaccine and then wait 1 month before taking Mayzent.

To make sure this medicine is safe for you, tell your doctor if you have ever had::

• weak immune system (caused by disease or by using certain medicines);

• fever or an active or chronic infection;

• high blood pressure;

• slow or irregular heart beats;

• heart problems, a heart attack, a stroke, or chest pain;

• asthma, sleep apnea (breathing stops during sleep), or other breathing disorder;

• skin cancer (melanoma);

• an eye condition called uveitis;

• diabetes; or

• liver disease.

Tell your doctor if you have recently received a vaccine, or if you are scheduled to receive a vaccine.

Siponimod may harm an unborn baby. Use effective birth control while using Mayzent and for at least 10 days after your last dose. Tell your doctor if you become pregnant .

If you are pregnant, your name may be listed on a pregnancy registry to track the effects of siponimod on the baby.

Ask a doctor if it is safe to breastfeed while using this medicine.

Call your doctor for instructions. If you miss 1 or more of your first doses, or 4 or more of your maintenance doses, you may need to take your next dose under medical observation in a medical setting.

Get your prescription refilled before you run out of medicine completely.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Avoid receiving a vaccine without asking your doctor. The vaccine may not work as well while you are using Mayzent. Receiving a "live" vaccine while using Mayzent may cause you to develop an infection. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

If you need to receive a vaccine, you should stop taking Mayzent for at least 1 week ahead of time. After receiving the vaccine, you should wait another 4 weeks before you start taking Mayzent again. Do not stop taking this medicine without your doctor's advice.

Always ask your doctor before you stop or start taking this medicine for any reason.

Get emergency medical help if you have signs of an allergic reaction to Mayzent: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Siponimod may cause serious side effects. Call your doctor at once if you have:

• slow or irregular heartbeats;

• vision problems such as increased sensitivity to light, blurred vision, eye pain, having a blind spot or shadows in the center of your vision, or unusual color to your vision (vision problems may occur 1 to 4 months after you start taking Mayzent);

• headache, confusion, change in mental status;

• a seizure;

• sores in your mouth and throat, cold sores, sores on your genital or anal area;

• skin changes, unusual moles that change in color or size;

• shortness of breath;

• liver problems - nausea, vomiting, upper stomach pain, tiredness, loss of appetite, dark urine, jaundice (yellowing of the skin or eyes); or

• symptoms of meningitis - fever, chills, body aches, tiredness, nausea and vomiting, neck stiffness, increased sensitivity to light.

Common Mayzent side effects may include:

• headache;

• increased blood pressure; or

• abnormal liver function tests.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Sometimes it is not safe to use certain medicines at the same time. Some drugs can affect your blood levels of other drugs you use, which may increase side effects or make the medicines less effective.

Siponimod can cause a serious heart problem. Your risk may be higher if you also use certain other medicines for infections, asthma, heart problems, high blood pressure, depression, mental illness, cancer, malaria, or HIV.

Siponimod can have long lasting effects on your body, especially on your immune system. For 3 or 4 weeks after your last dose, tell any doctor who treats you that you have used Mayzent.

Tell your doctor about all your current medicines. Many drugs can interact with siponimod, especially:

• drugs that weaken the immune system such as cancer medicine, steroids, and medicines to prevent organ transplant rejection;

• other medicines to treat MS symptoms; or

• heart medications.

This list is not complete and many other drugs may interact with siponimod. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.